Epstein Barr virus causes pulmonary edema. Dr. Komarovsky about Epstein Barr virus in children. How does infection occur in adults?

Definition and description of Epstein-Barr virus

Epstein-Barr viral infection - acute or chronic infection human, caused by the Epstein-Barr virus from the family of herpes viruses (Herpesviridae). It has the peculiarity of damaging the lymphoreticular and immune systems of the body (1.6).

Epstein-Barr virus (EBV) is a DNA virus from the Family Herpesviridae (gammaherpesviruses), and is a type 4 herpesvirus.

Epstein-Barr virus is a low-contagious infection, since many people have antibodies to this virus

Particularly noteworthy is the property of the Epstein-Barr virus, such as “lifelong persistence in the body.” Thanks to infection of B-lymphocytes, in which it is present for life, these cells of the immune system acquire the ability for unlimited life activity (so-called “cellular immortality”), as well as the ability to constantly synthesize heterophilic antibodies (or autoantibodies, for example, antinuclear antibodies, rheumatoid factor, cold agglutinins) (6).

The virus has a spherical shape with a diameter of up to 180 nm. The structure consists of 4 components: core, capsid (outermost shell), inner and outer shell.

The core contains two strands of DNA containing up to 80 genes. The viral particle on the surface also contains dozens of glycoproteins necessary for the formation of virus-neutralizing antibodies.

The viral particle contains the following specific antigens (proteins necessary for diagnosis):

• capsid antigen (VCA);
• early antigen (EA);
• nuclear or nuclear antigen (NA or EBNA);
• membrane antigen (MA).

The significance and timing of their appearance in different forms of EBVI are not the same and have their own specific meaning in terms of assessing the phase of the disease during a laboratory examination of the patient (6).

The Epstein-Barr virus is relatively stable in the external environment and dies quickly when dried out, exposed to high temperatures, and exposed to common disinfectants.

In biological tissues and fluids, the Epstein-Barr virus can feel beneficial when it enters the blood of a patient with EBVI, brain cells of a completely healthy person, cells during oncological processes (lymphoma, leukemia, and others).

The sources of infection for Epstein-Barr viral infection are a patient with a clinically pronounced form and a virus carrier.

The patient becomes infectious in last days incubation period, the initial period of the disease, the height of the disease, as well as the entire period of convalescence (up to 6 months after recovery), and up to 20% of those who have recovered retain the ability to periodically secrete the virus (that is, they remain carriers) (6,7).

Mechanisms of Epstein-Barr virus infection:

• this is an aerogenic (airborne transmission route), in which saliva and mucus from the oropharynx, which is released when sneezing, coughing, talking, kissing, is contagious;
• contact mechanism (contact-household transmission route), in which salivation of household items (dishes, toys, towels, etc.) occurs, but due to the instability of the virus in the external environment, it is of unlikely significance;
• a transfusion mechanism of infection is allowed (during the transfusion of infected blood and its preparations);
• nutritional mechanism (water-food transmission route);
• Currently, the transplacental mechanism of infection of the fetus with the possibility of developing congenital Epstein-Barr viral infection has been proven (1,6).

Despite the variety of routes of infection, there is a good immune layer among the population - up to 50% of children and 85% of adults are infected with this virus. Many become infected from carriers without developing symptoms of the disease, but with the development of immunity. That is why it is believed that if a patient is surrounded by an Epstein-Barr viral infection, the disease is less contagious, since many already have antibodies to the Epstein-Barr virus.

Infectious mononucleosis

Epstein-Barr virus can cause acute infection, chronic forms of infection, and asymptomatic carriage (7).

The classic manifestation of acute Epstein-Barr viral infection is infectious mononucleosis - this is an acute viral disease characterized by fever, damage to the pharynx, lymph nodes, liver, spleen and peculiar changes in the clinical blood test.

The clinical picture of the disease was first described in 1885 by N. F. Filatov and was considered as idiopathic inflammation of the lymph glands.

The connection of the disease with Epstein-Barr virus was proven in the late 1960s (1, 10). The disease develops predominantly in young adults, but it can occur in all patients from children to the elderly. The incubation period is 5-12 days, but can reach 30-45 days; as a rule, it is not possible to associate the disease with contact with a patient.

The disease is accompanied by an increase in temperature to 38-39 degrees, although in some patients the disease occurs at normal temperature. The duration of the febrile period can reach 1 month or more.

Enlarged lymph nodes (viral lymphadenitis) is the most constant symptom of the disease. The lymph nodes in the head and neck area enlarge earlier than others and most clearly; bilateral enlargement of the lymph nodes is typical; unilateral lesions are rare.

Less commonly, the axillary, inguinal, ulnar lymph nodes, lymph nodes of the mediastinum and abdominal cavity are involved in the process. The most striking and characteristic sign of infectious mononucleosis is damage to the pharynx, which develops from the first days of the disease, sometimes later.

Sore throat in infectious mononucleosis can be different in form and in some cases even accompanied by the formation of fibrinous films reminiscent of diphtheria. Characterized by a pronounced enlargement of the palatine tonsils, the presence of small hemorrhages (petechiae) on back wall pharynx, which distinguishes the disease from other viral pharyngitis, but not from streptococcal sore throat, swelling of the uvula may occur. Often the nasopharyngeal tonsil is involved in the process, causing patients to experience difficulty in nasal breathing, nasal sounds and snoring during sleep.

If you have an elevated temperature and enlarged lymph nodes, you should first consult a therapist.

An enlarged liver and spleen are natural manifestations of the disease. Liver dysfunction - moderate yellowness of the sclera, changes in biochemical blood tests are more typical for older people. Rarely (in 3-25% of patients) a skin rash may occur - maculopapular, hemorrhagic, roseola, or miliaria-type rash (1.10).

Observed characteristic changes in a clinical blood test - moderate leukocytosis, a decrease in the number of neutrophils, lymphocytosis and the appearance of specific cells - atypical mononuclear cells, appearing on the 2-3rd day of the disease and persisting up to 4 weeks (1.10).

To diagnose the disease, in addition to general and biochemical blood tests, specific serological diagnostics are used - determination of IgG and IgM antibodies to the capsid proteins of the Epstein-Barr virus.

So-called heterophilic antibodies are also determined - autoantibodies that are synthesized by infected B lymphocytes. These include antinuclear antibodies, rheumatoid factor, cold agglutinins.

For treatment, antiviral drugs from the group of acyclic nucleosides, interferon preparations and interferon inducers are used. Symptomatic treatment of existing disorders of internal organs is carried out.

Rarely, when there is a pronounced enlargement of the tonsils or a number of complications occur, glucocorticosteroids are used.

The patient is hospitalized according to clinical indications.

For of this disease Anti-epidemic measures are not carried out, specific prevention has not been developed (1.7, 8, 10).

Chronic forms of Epstein-Barr viral infection

Chronic EBV-infection develops no earlier than 6 months after an acute infection, and in the absence of a history of acute mononucleosis - 6 or more months after infection. Often, the latent form of infection with a decrease in immunity turns into a chronic infection. Chronic EBV infection can occur in the form of: chronic active EBV infection, hemophagocytic syndrome associated with EBV, atypical forms of EBV (recurrent bacterial, fungal and other infections digestive system, respiratory tract, skin and mucous membranes) (7).

Chronic active EBV infection is characterized by a long course and frequent relapses.

Symptoms

• weakness,
• increased fatigue,
• excessive sweating,
• long-term slight fever up to 37.2-37.5°,
• skin rashes,
• sometimes articular syndrome,
• pain in the muscles of the trunk and limbs,
• heaviness in the right hypochondrium,
• feeling of discomfort in the throat area,
• slight cough
• nasal congestion,
• some patients have neurological disorders - causeless headaches, memory impairment, sleep disturbances, frequent shifts mood, tendency to depression, patients are inattentive, decreased intelligence.
• Patients often complain of enlargement of one or a group of lymph nodes, and possibly enlargement of internal organs (spleen and liver).

Along with such complaints, when questioning the patient, it becomes clear that there have been frequent cold infections, fungal diseases, and other herpetic diseases recently. For example, simple herpes on the lips or genital herpes and more.

In confirmation of clinical data there will also be laboratory signs (blood changes, immune status, specific tests for antibodies).

Hemophagocytic syndrome associated with EBV manifests itself in the form of anemia or pancytopenia (a decrease in the composition of almost all blood elements associated with inhibition of hematopoietic germs).

Patients may experience fever (wavy or intermittent, in which both sudden and gradual rises in temperature are possible with restoration to normal values), enlargement of the lymph nodes, liver and spleen, impaired liver function, laboratory changes in the blood in the form of a decrease in both red blood cells and and leukocytes and other blood elements.

Erased (atypical) forms of Epstein-Barr viral infection: most often it is a fever of unknown origin lasting for months, years, accompanied by enlarged lymph nodes, sometimes joint manifestations, muscle pain; another option is secondary immunodeficiency with frequent viral, bacterial, fungal infections (7)

Considering all of the above, doctors refer patients with prolonged fever or lymphadenopathy for consultation with an allergist-immunologist to exclude erased forms of Epstein-Barr viral infection. However, consultation with this specialist is necessary only after excluding other causes that have a more serious prognosis (oncological diseases, tuberculosis, etc.) or are more common (chronic foci of bacterial infection).

If there is a prolonged increase in temperature or enlarged and painful lymph nodes, the examination should begin with a consultation with a physician (5).

One of the forms of chronic Epstein-Barr virus infection is the so-called “syndrome chronic fatigue"- a condition characterized by constant fatigue that does not go away after a long and proper rest.

Patients with chronic fatigue syndrome are characterized by muscle weakness, periods of apathy, depressive states, mood lability, irritability, and sometimes outbursts of anger and aggression.

Patients are lethargic, complain of memory impairment, decreased intelligence. Patients sleep poorly, and both the phase of falling asleep is disrupted and intermittent sleep is observed, insomnia and drowsiness are possible during the day. At the same time, autonomic disorders are characteristic: trembling or tremor of the fingers, sweating, periodically low temperature, poor appetite, joint pain.

The disease can develop at any age, and women predominate among patients. At risk are workaholics, people with increased physical and mental work, people in both acute stressful situations and chronic stress.

There is a high prevalence of the syndrome among ethnic and racial minorities and people with low socioeconomic status.

Unfortunately, even foreign publications do not mention enough serious attitude to patient complaints in this condition and non-recognition of chronic fatigue syndrome as a real problem caused by a biological process (7, 11).

To diagnose chronic forms of Epstein-Barr virus infection, in addition to the above-mentioned serological tests, determination of viral DNA by PCR in blood, saliva, oropharyngeal swabs and other biological materials, and assessment of immune status are used (8, 9).

Complications and severe forms of diseases caused by the Epstein-Barr virus

Acute and chronic forms of Epstein-Barr virus infection can lead to serious complications. In addition, the infection itself, under certain circumstances, can occur in the form of diseases with a serious prognosis for life and health.

Thus, with infectious mononucleosis, excessive enlargement of the palatine tonsils is possible, which can lead to obstruction of the upper respiratory tract, rupture of the spleen, and in rare cases, encephalitis, lymphoma.

In children, Epstein-Barr virus infection can lead to the development of a fulminant form of hepatitis with the development of acute liver failure, but the incidence of this complication is very low (13).

For older patients, liver damage from infectious mononucleosis can lead to cholestasis (10).

In countries with tropical and subtropical climates, Epstein-Barr viral infection can cause the development of malignant neoplasms (Burkitt's lymphosarcoma - aggressive B-cell, nasopharyngeal carcinoma and others), often with metastases to various organs (6, 15).

In countries with temperate climates, in addition to the infectious mononucleosis and chronic forms of infection described above, the Epstein-Barr virus can cause the development autoimmune diseases(rheumatic diseases, vasculitis, nonspecific ulcerative colitis) (6).

A rare complication of Epstein-Barr viral infection is viral arthritis, which manifests itself as polyarthralgia or, much less commonly, monoarthritis of the knee joint, the formation of a Baker's cyst with possible rupture (14).

Effect of Epstein-Barr virus on the immune system

Damage to the immune system by Epstein-Barr virus is an integral part of the pathogenesis of Epstein-Barr virus infection.

It was discovered that the Epstein-Barr virus has a large set of genes that give it the ability to evade the human immune system to a certain extent. In particular, it produces proteins that are analogues of a number of human interleukins and their receptors that modify the immune response.

During the period of active reproduction, the virus produces interleukin - a 10-like protein that suppresses T-cell immunity, the function of cytotoxic lymphocytes, macrophages, and disrupts all stages of the functioning of natural killer cells (that is, the most important antiviral defense systems).

Another viral protein (BI3) can also suppress T-cell immunity and block killer cell activity (via suppression of interleukin-12).

Another property of the Epstein-Barr virus, like other herpes viruses, is its high mutability, which allows it to avoid the effects of specific antibodies (accumulated to the virus before its mutation) and host immune system cells for a certain time (7). Thus, the reproduction of the Epstein-Barr virus in the human body can cause the occurrence of infection, manifested by the addition of other herpetic, bacterial and fungal infections. For example, herpes labialis, genital herpes, thrush, inflammatory diseases upper respiratory tract and gastrointestinal tract.

On the other hand, the course of this infection in patients with secondary immunodeficiency contributes to a more severe course of infection, the development of chronic forms, and the occurrence of complications.

Classic examples of severe forms of Epstein-Barr virus infection in patients with secondary immunodeficiency occur in HIV-infected patients. In this group of patients, the infection occurs in the form of specific forms:

• “Hairy leukoplakia” of the tongue and oral mucosa, in which whitish folds appear on the lateral surfaces of the tongue, as well as on the mucous membrane of the cheeks and gums, which gradually merge, forming white plaques with a heterogeneous surface, as if covered with grooves, cracks and erosive surfaces form. As a rule, there is no pain with this disease.
• Lymphoid interstitial pneumonia, which is a polyetiological disease (there is also a connection with Epstein-Barr viral infection) and is characterized by shortness of breath, unproductive cough against the background of fever and symptoms of intoxication, as well as progressive weight loss of patients. The patient has an enlarged liver and spleen, lymph nodes, and enlarged salivary glands. X-ray examination revealed bilateral lower lobe interstitial foci of inflammation lung tissue, roots are expanded, unstructured.
• In persons with severe immune deficiency, generalized forms of EBV infection may occur with damage to the central and peripheral nervous systems (the development of meningitis, encephalitis, cerebellar ataxia, polyradiculoneuritis), as well as damage to other internal organs (the development of myocarditis, glomerulonephritis, lymphocytic interstitial pneumonitis, severe forms of hepatitis). Generalized forms of EBV infection are often fatal (7).

Also, Epstein-Barr virus infection can cause the occurrence of lymphoproliferative diseases in transplanted organs after transplantation and subsequent immunotherapy in individuals who have not been exposed to the Epstein-Barr virus before transplantation and do not have immunity to it at the time of intervention (12).

Epstein-Barr virus infection and pregnancy

IN last years The transplacental mechanism of infection of the fetus has been proven and a congenital Epstein-Barr virus infection has been described, which occurs in the fetus during the primary infection of a pregnant woman with the Epstein-Barr virus.

It has been established that its risk with primary EBVI during pregnancy is 67%, with reactivation - 22%.

It is characterized by possible damage to the internal organs of the child in the form of interstitial pneumonia, encephalitis, myocarditis and others. Prematurity and premature birth are possible.

Both maternal antibodies to the Epstein-Barr virus (IgG to EBNA, VCA, EA antigens) and clear confirmation of intrauterine infection - the child’s own antibodies (IgM to EA, IgM to VCA antigens of the virus) can circulate in the blood of a born baby (7).

The influence of Epstein-Barr virus on the course of allergic diseases

Since the immune system is involved in the pathogenesis of Epstein-Barr viral infection, the virus may influence the occurrence of a number of allergic diseases.

A classic example of the debut of an allergic disease with an Epstein-Barr viral infection is the occurrence of a generalized one when taking penicillin antibiotics to treat tonsillitis caused by the Epstein-Barr virus.

The appearance of a rash to aminopenicillins is not an IgE-dependent reaction, so the use has neither a preventive nor a therapeutic effect. After recovery, repeated reactions to penicillin antibiotics may not be observed. It is possible to develop erythema multiforme exudate, in severe cases - Stevens-Johnson syndrome and. The latter cases are characterized by an extremely severe course and a high risk of death (2). Therefore, it is very dangerous to take penicillin antibiotics on your own for a sore throat without a preliminary medical examination and a general blood test.

In recent years, the possible influence of the Epstein-Barr virus on the occurrence of chronic relapsing disease has been studied (4). The possibility of the development of exudative erythema multiforme against the background of Epstein-Barr viral infection has been shown, regardless of the use of medications (16).

Epstein-Barr virus infection (EBVI) is one of the common human diseases. According to WHO, about 55-60% of young children (under 3 years old) are infected with the Epstein-Barr virus; the vast majority of the adult population of the planet (90-98%) have antibodies to EBV. The incidence in different countries of the world ranges from 3-5 to 45 cases per 100 thousand population and is a fairly high indicator. EBVI belongs to the group of uncontrollable infections for which there is no specific prevention (vaccination), which certainly affects the incidence rate.

Epstein-Barr viral infection– an acute or chronic infectious disease of humans caused by the Epstein-Barr virus from the family of herpetic viruses (Herpesviridae), which has a favorite feature of damaging the lymphoreticular and immune systems of the body.

Pathogen EBVI

Epstein-Barr virus (EBV) is a DNA virus from the Family Herpesviridae (gamma herpesviruses), is a type 4 herpesvirus. It was first identified from Burkett's lymphoma cells about 35-40 years ago.
The virus has a spherical shape with a diameter of up to 180 nm. The structure consists of 4 components: core, capsid, inner and outer shell. The core includes DNA, consisting of 2 strands, including up to 80 genes.

The viral particle on the surface also contains dozens of glycoproteins necessary for the formation of virus-neutralizing antibodies. The viral particle contains specific antigens (proteins necessary for diagnosis):

Capsid antigen (VCA);
- early antigen (EA);
- nuclear or nuclear antigen (NA or EBNA);
- membrane antigen (MA).

The significance and timing of their appearance in different forms of EBVI are not the same and have their own specific meaning.

The Epstein-Barr virus is relatively stable in the external environment and dies quickly when dried out, exposed to high temperatures, and exposed to common disinfectants. In biological tissues and fluids, the Epstein-Barr virus can feel beneficial when it enters the blood of a patient with EBVI, brain cells of a completely healthy person, cells during oncological processes (lymphoma, leukemia and others).

The virus has a certain tropism (tendency to infect favorite cells):

1) affinity for cells of the lymphoreticular system(damage to lymph nodes of any group occurs, enlargement of the liver and spleen);
2) affinity for cells of the immune system(the virus multiplies in B-lymphocytes, where it can persist for life, as a result of which their functional state is disrupted and immunodeficiency occurs); in addition to B-lymphocytes, EBVI also disrupts the cellular component of immunity (macrophages, NK - natural killer cells, neutrophils and others), which leads to a decrease in the body’s overall resistance to various viral and bacterial infections;
3) affinity for epithelial cells of the upper respiratory tract and digestive tract , due to which children may experience respiratory syndrome (cough, shortness of breath, “false croup”), diarrhea syndrome (loose stools).

Epstein-Barr virus has allergenic properties, which manifests itself in certain symptoms in patients: 20-25% of patients have an allergic rash, some patients may develop Quincke's edema.

Particular attention is paid to such a property of the Epstein-Barr virus as “ lifelong persistence in the body" Thanks to infection of B-lymphocytes, these cells of the immune system acquire the ability for unlimited life activity (so-called “cellular immortality”), as well as the constant synthesis of heterophilic antibodies (or autoantibodies, for example, antinuclear antibodies, rheumatoid factor, cold agglutinins). EBV lives in these cells permanently.

Currently, strains 1 and 2 of the Epstein-Barr virus are known, which do not differ serologically.

Causes of Epstein-Barr viral infection

Source of infection for EBVI– a patient with a clinically expressed form and a virus carrier. The patient becomes infectious in the last days of the incubation period, the initial period of the illness, the height of the disease, as well as the entire period of convalescence (up to 6 months after recovery), and up to 20% of those who have recovered retain the ability to periodically secrete the virus (that is, they remain carriers).

Mechanisms of EBVI infection:
– this is an aerogenic (airborne transmission route), in which saliva and mucus from the oropharynx, which is released when sneezing, coughing, talking, kissing, is contagious;
- contact mechanism (contact-household transmission route), in which salivation of household items (dishes, toys, towels, etc.) occurs, but due to the instability of the virus in the external environment, it is of unlikely significance;
- a transfusion mechanism of infection is allowed (during transfusion of infected blood and its preparations);
- nutritional mechanism (water-food transmission route);
- the transplacental mechanism of infection of the fetus with the possibility of developing congenital EBVI has now been proven.

Susceptibility to EBVI: Infants (up to 1 year) rarely suffer from Epstein-Barr viral infection due to the presence of passive maternal immunity (maternal antibodies), the most susceptible to infection and the development of a clinically pronounced form of EBVI are children from 2 to 10 years of age.

Despite the variety of routes of infection, there is a good immune layer among the population (up to 50% of children and 85% of adults): many become infected from carriers without developing symptoms of the disease, but with the development of immunity. This is why it is believed that the disease is less contagious to those around an EBVI patient, since many already have antibodies to the Epstein-Barr virus.

Rarely in institutions closed type(military units, dormitories) outbreaks of EBVI can still be observed, which are low-intensity in severity and also extended over time.

EBVI, and in particular its most common manifestation - mononucleosis - is characterized by spring-autumn seasonality.
Immunity after an infection is formed lasting and lifelong. Get sick again acute form EBVI is not allowed. Repeated cases of the disease are associated with the development of a relapse or chronic form of the disease and its exacerbation.

The path of the Epstein-Barr virus in the human body

Entrance gates of infection– mucous membrane of the oropharynx and nasopharynx, where the virus multiplies and nonspecific (primary) defense is organized. The outcomes of primary infection are influenced by: general immunity, concomitant diseases, condition entrance gate infections (whether there are chronic diseases of the oropharynx or nasopharynx), as well as the infectious dose and virulence of the pathogen.

The outcomes of primary infection can be:

1) sanitation (destruction of the virus at the entrance gate);
2) subclinical (asymptomatic form);
3) clinically detectable (manifest) form;
4) primary latent form (in which virus reproduction and isolation are possible, but there are no clinical symptoms).

Next, from the entrance gate of the infection, the virus enters the blood (viremia) - the patient may have a fever and intoxication. At the site of the entrance gate, a “primary focus” is formed - catarrhal tonsillitis, difficulty in nasal breathing. Next, the virus is introduced into various tissues and organs with primary damage to the liver, spleen, lymph nodes and others. It is during this period that “atypical tissue mononuclear cells” appear in the blood against the background of a moderate increase in lymphocytes.

The outcomes of the disease can be: recovery, chronic EBV infection, asymptomatic carriage, autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, Sjogren's syndrome and others), oncological diseases, with oncological diseases and congenital EBV infection – death is possible.

Symptoms of EBV infection

Depending on the climate, certain clinical forms of EBVI predominate. In countries with a temperate climate, which includes the Russian Federation, infectious mononucleosis is more common, and if there is no deficiency of immunity, a subclinical (asymptomatic) form of the disease can develop. Also, the Epstein-Barr virus can cause “chronic fatigue syndrome” and autoimmune diseases (rheumatic diseases, vasculitis, ulcerative colitis). In countries with tropical and subtropical climates, the development of malignant neoplasms (Burkitt's lymphosarcoma, nasopharyngeal carcinoma and others) is possible, often with metastases to various organs. In HIV-infected patients, EBVI is associated with hairy leukoplakia of the tongue, brain lymphoma, and other manifestations.

Currently, the direct connection of the Epstein-Barr virus with the development of acute mononucleosis, chronic EBV (or EBV infection), congenital EBV infection, “chronic fatigue syndrome”, lymphoid interstitial pneumonia, hepatitis, oncological lymphoproliferative diseases (Burkitt’s lymphoma, T-cell lymphoma, nasopharyngeal carcinoma or NFC, leiomyosarcoma, non-Hodgin lymphomas), HIV-associated diseases (hairy leukoplakia, brain lymphoma, common lymph node neoplasms).

More information about some manifestations of EBV infection:

1. Infectious mononucleosis, which manifests itself as an acute form of the disease with cyclicity and specific symptoms(fever, catarrhal tonsillitis, difficulty in nasal breathing, enlarged groups of lymph nodes, liver, spleen, allergic rash, specific changes in the blood). For more details, see the article “Infectious mononucleosis”.
Signs unfavorable for the development of chronic EBV infection:

Protracted nature of the infection (long-term low-grade fever - 37-37.5° - up to 3-6 months, persistence of enlarged lymph nodes for more than 1.5-3 months);
- the occurrence of relapses of the disease with the resumption of symptoms of the disease within 1.5-3-4 months after the initial attack of the disease;
- persistence of IgM antibodies (to EA, VCA EBV antigens) for more than 3 months from the onset of the disease; absence of seroconversion (seroconversion is the disappearance of IgM antibodies and the formation of IgG antibodies in different antigens of the Epstein-Barr virus);
- untimely initiation or complete absence of specific treatment.

2. Chronic EBV infection forms no earlier than 6 months after an acute infection, and in the absence of a history of acute mononucleosis - 6 or more months after infection. Often, the latent form of infection with a decrease in immunity turns into a chronic infection. Chronic EBV infection can occur in the form of: chronic active EBV infection, hemophagocytic syndrome associated with EBV, atypical forms of EBV (recurrent bacterial, fungal and other infections of the digestive system, respiratory tract, skin and mucous membranes).

Chronic active EBV infection characterized by a long course and frequent relapses. Patients are concerned about weakness, increased fatigue, excessive sweating, prolonged low temperature up to 37.2-37.5°, skin rashes, sometimes joint syndrome, pain in the muscles of the trunk and limbs, heaviness in the right hypochondrium, discomfort in the throat, slight cough and nasal congestion, some patients have neurological disorders - causeless headaches, memory impairment, sleep disturbances, frequent mood swings, a tendency to depression, patients are inattentive, decreased intelligence. Patients often complain of enlargement of one or a group of lymph nodes, and possibly enlargement of internal organs (spleen and liver).
Along with such complaints, when questioning the patient, it becomes clear that there have been frequent cold infections, fungal diseases, and the addition of other herpetic diseases (for example, herpes simplex on the lips or genital herpes, etc.).
To confirm the clinical data, there will also be laboratory signs (changes in blood, immune status, specific tests for antibodies).
With a pronounced decrease in immunity during chronic active EBV infection, the process generalizes and damage to internal organs is possible with the development of meningitis, encephalitis, polyradiculoneuritis, myocarditis, glomerulonephritis, pneumonia and others.

Hemophagocytic syndrome associated with EBV manifests itself in the form of anemia or pancytopenia (a decrease in the composition of almost all blood elements associated with inhibition of hematopoietic germs). Patients may experience fever (wavy or intermittent, in which both sudden and gradual rises in temperature are possible with restoration to normal values), enlargement of the lymph nodes, liver and spleen, impaired liver function, laboratory changes in the blood in the form of a decrease in both red blood cells and and leukocytes and other blood elements.

Erased (atypical) forms of EBVI: most often this is a fever of unknown origin that lasts for months, years, accompanied by enlarged lymph nodes, sometimes joint manifestations, muscle pain; Another option is secondary immunodeficiency with frequent viral, bacterial, and fungal infections.

3. Congenital EBV infection occurs in the presence of an acute form of EBV or chronic active EBV infection that occurs during the mother’s pregnancy. It is characterized by possible damage to the internal organs of the child in the form of interstitial pneumonia, encephalitis, myocarditis and others. Prematurity and premature birth are possible. Both maternal antibodies to the Epstein-Barr virus (IgG to EBNA, VCA, EA antigens) and clear confirmation of intrauterine infection - the child’s own antibodies (IgM to EA, IgM to VCA antigens of the virus) can circulate in the blood of a born baby.

4. " Chronic fatigue syndrome“characterized by constant fatigue that does not go away after a long and proper rest. Patients with chronic fatigue syndrome are characterized by muscle weakness, periods of apathy, depressive states, mood lability, irritability, and sometimes outbursts of anger and aggression. Patients are lethargic, complain of memory impairment, decreased intelligence. Patients sleep poorly, and both the phase of falling asleep is disrupted and intermittent sleep is observed, insomnia and drowsiness are possible during the day. At the same time, autonomic disorders are characteristic: trembling or tremor of the fingers, sweating, periodically low temperature, poor appetite, joint pain.
At risk are workaholics, people with increased physical and mental work, people in both acute stressful situations and chronic stress.

5. HIV-associated diseases
"Hairy leukoplakia" tongue and oral mucosa appears with severe
immunodeficiency, often associated with HIV infection. On the lateral surfaces of the tongue, as well as on the mucous membrane of the cheeks and gums, whitish folds appear, which gradually merge, forming white plaques with a heterogeneous surface, as if covered with grooves, cracks and erosive surfaces form. As a rule, there is no pain with this disease.

Lymphoid interstitial pneumonia is a polyetiological disease (there is a connection with pneumocystis, as well as with EBV) and is characterized by shortness of breath, unproductive cough
against the background of fever and symptoms of intoxication, as well as progressive weight loss of patients. The patient has an enlarged liver and spleen, lymph nodes, and enlarged salivary glands. X-ray examination showed bilateral lower lobe interstitial foci of inflammation of the lung tissue, the roots were expanded and non-structural.

6. Oncological lymphoproliferative diseases(Burkitt's lymphoma, nasopharyngeal carcinoma - NFC, T-cell lymphoma, non-Hodgin's lymphoma and others)

Diagnosis of Epstein-Barr viral infection

1. Preliminary diagnosis is always set on the basis of clinical and epidemiological data. Suspicion of EBVI is confirmed by clinical laboratory tests, in particular a complete blood count, which can reveal indirect signs of viral activity: lymphomonocytosis (increase in lymphocytes, monocytes), less commonly, monocytosis with lymphopenia (increase in monocytes with a decrease in lymphocytes), thrombocytosis (increase in platelets), anemia (decrease in red blood cells and hemoglobin), the appearance of atypical mononuclear cells in the blood.

Atypical mononuclear cells (or virocytes)- these are modified lymphocytes, which, according to morphological characteristics, have some similarities with monocytes. These are mononuclear cells, are young cells, appear in the blood to fight viruses. It is the latter property that explains their appearance in EBVI (especially in its acute form). The diagnosis of infectious mononucleosis is considered confirmed if the presence of atypical mononuclear cells in the blood is more than 10%, but their number can range from 10 to 50% or more.

For the qualitative and quantitative determination of atypical mononuclear cells, the leukocyte concentration method is used, which is a highly sensitive method.

Dates of appearance: Atypical mononuclear cells appear in the first days of the disease, at the height of the disease their number is maximum (40-50% or more), in some patients their appearance is recorded a week after the onset of the disease.

Duration of their detection: in most patients, atypical mononuclear cells continue to be detected within 2-3 weeks from the onset of the disease, in some patients they disappear by the beginning of the 2nd week of the disease. In 40% of patients, detection of atypical mononuclear cells in the blood continues for up to a month or more (in this case, it makes sense to carry out active prevention of chronicity of the process).

Also, at the preliminary diagnosis stage, a biochemical study of blood serum is carried out, which shows signs of liver damage (slight increase in bilirubin, increased enzyme activity - ALT, AST, GGTP, thymol test).

2. Final diagnosis is determined after specific laboratory tests.

1) Heterophilic test– detection of heterophilic antibodies in blood serum, detected in the vast majority of patients with EBVI. Is additional method diagnostics Heterophilic antibodies produced in response to EBV infection are autoantibodies that are synthesized by infected B lymphocytes. These include antinuclear antibodies, rheumatic factor, cold agglutinins. They belong to antibodies IgM class. They appear in the first 1-2 weeks from the moment of infection, and they are characterized by a gradual increase during the first 3-4 weeks, then a gradual decrease in the next 2 months and persistence in the blood throughout the entire period of convalescence (3-6 months). If this test is negative in the presence of symptoms of EBVI, it is recommended to repeat it after 2 weeks.
Conditions such as hepatitis, leukemia, lymphoma, drug use can give a false positive result for heterophile antibodies. narcotic drugs. Antibodies of this group can also be positive for: systemic lupus erythematosus, cryoglobulinemia, syphilis.

2) Serological tests for antibodies to the Epstein-Barr virus using ELISA(linked immunosorbent assay).
IgM to VCA(to the capsid antigen) - detected in the blood in the first days and weeks of the disease, maximum by the 3-4th week of the disease, can circulate for up to 3 months, and then their number decreases to an undetectable value and disappears completely. Their persistence for more than 3 months indicates a protracted course of the disease. Found in 90-100% of patients with acute EBVI.
IgG to VCA(to the capsid antigen) - appear in the blood 1-2 months after the onset of the disease, then gradually decrease and remain at a threshold (low level) for life. An increase in their titer is characteristic of exacerbation of chronic EBVI.
IgM to EA(to early antigen) - appears in the blood in the first week of the disease, persists for 2-3 months and disappears. Found in 75-90% of patients. Maintaining high titers for a long time (more than 3-4 months) is alarming in terms of the formation of a chronic form of EBVI. Their appearance during chronic infection serves as an indicator of reactivation. They can often be detected during primary infection in EBV carriers.
IgG to EA(to the early antigen) - appear by the 3-4th week of the disease, become maximum at 4-6 weeks of the disease, disappear after 3-6 months. The appearance of high titers again indicates activation of a chronic infection.
IgG to NA-1 or EBNA(to nuclear or nuclear antigen) - are late, since they appear in the blood 1-3 months after the onset of the disease. For a long time (up to 12 months) the titer is quite high, and then the titer decreases and remains at a threshold (low) level for life. In young children (up to 3-4 years old), these antibodies appear late - 4-6 months after infection. If a person has severe immunodeficiency (stage of AIDS due to HIV infection, oncological processes, etc.), then these antibodies may not be present. Reactivation of a chronic infection or relapse of acute EBVI is observed with high titers of IgG to the NA antigen.

Schemes for decoding results

Rules quality diagnostics EBV infections:

Dynamic laboratory testing: in most cases, a single antibody test is not enough to make a diagnosis. Repeated studies are required after 2 weeks, 4 weeks, 1.5 months, 3 and 6 months. The dynamic research algorithm and its necessity are determined only by the attending doctor!
- compare results made in one laboratory.
- there are no general standards for antibody titers; The result is assessed by the doctor in comparison with the reference values ​​of a specific laboratory, after which a conclusion is made how many times the required antibody titer is increased compared to the reference value. The threshold level, as a rule, does not exceed a 5-10-fold increase. High titers are diagnosed at 15-30x magnification and higher.

3) PCR diagnostics of EBV infection– qualitative detection of Epstein-Barr virus DNA using PCR.
The material for research is saliva or oral and nasopharyngeal mucus, scrapings of epithelial cells of the urogenital tract, blood, cerebrospinal fluid, prostate secretion, and urine.
Both patients with EBVI and carriers can have a positive PCR. Therefore, to differentiate them, PCR analysis is carried out with a given sensitivity: for carriers up to 10 copies in the sample, and for active infection - 100 copies in the sample. In young children (up to 1-3 years old), due to insufficiently developed immunity, diagnosis by antibodies is difficult, so in this group of patients PCR analysis comes to the rescue.
The specificity of this method is 100%, which practically eliminates false positive results. However, due to the fact that PCR analysis is informative only when the virus multiplies (replicates), there is a certain percentage of false negative results (up to 30%) associated precisely with the lack of replication at the time of the study.

4) Immunogram or immunological blood test.

With EBVI, there are two types of changes in immune status:

Increasing its activity (increasing the level of serum interferon, IgA, IgM, IgG, increasing CEC, increasing CD16+ - natural killer cells, increasing either T-helper CD4+ or T-suppressor CD8+)
Immune dysfunction or deficiency (decreased IgG, increased IgM, decreased antibody avidity, decreased CD25+ lymphocytes, decreased CD16+, CD4+, CD8, decreased phagocyte activity).

Treatment of EBV infection

1) Organizational and routine measures include hospitalization in an infectious diseases clinic for patients with an acute form of EBVI, depending on the severity. Patients with reactivation of a chronic infection are often treated on an outpatient basis. Diet therapy comes down to a complete diet with mechanical, chemical sparing of the digestive tract.

2) Drug specific therapy for EBVI.
Antiviral drugs (isoprinosine from the first days of life, Arbidol from 2 years, Valtrex from 2 years, Famvir from 12 years, acyclovir from the first days of life in the absence of other drugs, but much less effective).
Interferon preparations (viferon from the first days of life, kipferon from the first days of life, reaferon EC-lipind over 2 years, interferons for parenteral administration over 2 years old).
Interferon inducers (cycloferon over 4 years, neovir from the first days of life, amiksin from 7 years, anaferon from 3 years).

Rules for specific therapy for EBVI:
1) All medications, doses, courses are prescribed exclusively by the attending doctor.
2) After the main course of treatment, a long maintenance course is required.
3) Combinations of immunomodulators are prescribed with caution and only by a doctor.
3) Drugs to enhance the intensity of treatment.

Immunocorrection (after immunogram examination) – immunomodulators (thymogen, polyoxidonium, derinat, lycopid, ribomunil, immunorix, roncoleukin and others);
- Hepatoprotectors (karsil, gepabene, hepatofalk, essentiale, heptral, ursosan, ovesol and others);
- Enterosorbents (white coal, filtrum, lactofiltrum, enterosgel, smecta);
- Probiotics (Bifidum-Forte, Probifor, Biovestin, Bifiform and others);
- Antihistamines(Zyrtec, Claritin, Zodak, Erius and others);
- Other drugs according to indications.

Clinical examination of patients with acute and chronic forms of EBVI

All clinical observation is carried out by an infectious disease specialist, or in pediatric practice, in the absence of one, by an immunologist or pediatrician. After infectious mononucleosis, observation is established for 6 months after the illness. Examinations are carried out monthly, if necessary, consultations with narrow specialists: hematologist, immunologist, oncologist, ENT doctor and others
Laboratory tests are carried out quarterly (once every 3 months), and if necessary more often, a general blood test is carried out monthly for the first 3 months. Laboratory tests include: general blood test, antibody tests, PCR study of blood and oropharyngeal mucus, biochemical blood test, immunogram, ultrasound examination and others as indicated.

Prevention of Epstein-Barr viral infection

There is no specific prevention (vaccination). Preventive measures boil down to strengthening the immune system, hardening children, taking precautions when a sick person appears in the environment, and observing the rules of personal hygiene.

Infectious disease doctor N.I. Bykova

Professor Michael Epstein and his graduate student Yvonne Barr described a virus relatively recently - in 1964 - which was given a double name after their last names - Epstein-Barr. Despite the fact that this is one of the most common microorganisms of the herpes species, it is still “overlooked” by attention.

Danger of Epstein-Barr virus

This microorganism was isolated from biopsies of lymphoma tumors taken from children from African countries.

The difference between this virus and its “brothers” is that it encodes 85 proteins. For comparison: a virus herpes simplex encodes only 20. The virus attaches to the cell using a special structure - on its surface there is a large number of glycoproteins that ensure reliable penetration into the mucosa.

Once the virus enters the body, it remains for life and infects 90% of the human population. It is transmitted through contacts, during operations - through blood and bone marrow - and by airborne droplets.

But in most cases, the Epstein-Barr virus is transmitted to children through kisses from infected adults. The danger of this pathogenic flora does not lie in its penetration into the body, but in the fact that it provokes malignant processes and causes diseases that can cause serious complications in people with a reduced immune status. One of the diseases that occurs when the Epstein-Barr virus is introduced is infectious mononucleosis or Filatov's disease.

An increase in its activity causes the following diseases:

• chronic fatigue syndrome;
• systemic hepatitis;
• lymphogranulomatosis;
• lymphomas;
• multiple sclerosis;
• hairy leukoplakia of the oral cavity and some others.

Epstein-Barr symptoms

The characteristic symptoms of the Epstein-Barr virus depend on the disease that it provoked, but general signs indicate its introduction.

For example, infectious mononucleosis causes the following symptoms:

1. increased fatigue;
2. signs of pharyngitis;
3. temperature rise above febrile – more than 39º;
4. by days 5-7, the lymph nodes enlarge, starting with the cervical ones;
5. the spleen increases in size, sometimes the liver;
6. urine darkens;
7. the rash is heterogeneous in nature - urticaria, papules with liquid, roseola appear simultaneously.

Similar symptoms occur with chronic infection of the Epstein-Barr virus, the only thing is that during it the function of nasal breathing is impaired and mental abilities are reduced.

Against the background of the disease caused by this virus, the introduction of pathogenic flora of a different type begins and secondary infection occurs, candidiasis, stomatitis, inflammatory diseases of the upper and lower respiratory tract and digestive organs may begin.

Consequences of the EPSTEIN-BARR VIRUS

Infectious mononucleosis can be mild or severe; in some cases, it goes away without treatment after 4 months.

But the introduction of the virus sometimes causes severe complications that appear after the disease:

• encephalitis and meningitis;
• obstruction of the bronchopulmonary tree;
• general damage to the nervous system
• hepatitis;
• damage to the cranial nerves;
• pericarditis;
• myocarditis.

These diseases occur more often in children, since adults suffered from mononucleosis in childhood. In whatever form the diseases caused by the introduction of the virus occur.

Epstein-Barr - acute or chronic - they need to be treated. This is the only way to avoid complications.

Diagnosis of EPSTEIN-BARR VIRUS

To detect the Epstein-Barr virus in the body, the following laboratory diagnostic tests are used.

1. IN general analysis blood, the number of leukocytes, monocytes and lymphocytes is calculated - if infected, their number exceeds the norm;
2. Biochemical analysis - enzyme indicators AST, LDH and ALT are increased;
3. The state of the immune system is assessed: the production of interferon, immunoglobulins, etc. is specified;
4. Serological diagnostics are carried out - in time, antibodies to the Epstein-Barr virus are detected. IgM titers are determined. They are elevated during the clinical picture caused by mononucleosis, but also remain high after recovery - immunity against this virus lasts for life;
5. During DNA diagnostics, it is determined whether there are antibodies in physiological fluids: saliva, smears from the upper respiratory tract, spinal cord;
6. With the culture method, the spread of the virus is established - it is grown on brain cells, cells of patients with leukemia, etc.

Research allows not only to find viral particles in the blood, but also to determine the degree of damage to the body and predict the risk of complications.

Treatment of Epstein-Barr virus

There is no specific scheme according to which treatment is carried out. Each case requires its own therapeutic approach.

All patients suspected of infectious mononucleosis must be hospitalized.

• bed rest;
• increasing the amount of fluid you drink - drinks should be warm;
• respiratory manifestations are relieved with vasoconstrictor drops and rinses - solutions with antiseptics and folk remedies;
• decrease in temperature;
• vitamin therapy;
• antihistamines.

Therapy begins with the use of antiviral drugs of different groups: Arbidol, Valtrex, Acyclovir, interferons.

Antibiotics are included in therapeutic measures more often when a secondary infection occurs or respiratory conditions of acute severity.

Immunoglobulins used against the Epstein-Barr virus are one of the main drugs that help avoid complications after diseases caused by the introduction of this pathogenic flora. Immunoglobulin is administered by injection intravenously. The therapy is supplemented with drugs that increase the immune status of the body - immunomodulators and biological stimulants: Derinat, Likopid, cytokines, Actovegin...

If additional symptoms occur, they are eliminated according to individual schemes. They reduce the temperature with conventional antipyretics, when coughing, mucolytics and antitussive drugs are prescribed, otitis is treated with special drops, a runny nose - vasoconstrictor drugs local action.

The duration of the disease varies from 2-3 weeks to 3-4 months, it all depends on the severity of the symptoms.

Preventative measures for EPSTEIN-BARR VIRUS

It is impossible to prevent the introduction of the Epstein-Barr virus; it is necessary to try to create conditions so that the child’s body can endure the “meeting” with it as easily as possible and subsequently develop immunity for life. Children with normal immune status tolerate mononucleosis normally - it can even be asymptomatic.

What diseases can the Epstein-Barr virus cause? What symptoms are typical for EBV infection?

Are there changes in laboratory parameters strictly specific to EBV?

What does complex therapy for EBV infection include?

In recent years, there has been an increase in the number of patients suffering from chronic recurrent infections, which in many cases are accompanied by a pronounced disturbance in general well-being and a number of therapeutic complaints. The most widespread in clinical practice (most often caused by Herpes Simplex I), (Herpes zoster) and (most often caused by Herpes simplex II); In transplantology and gynecology, diseases and syndromes caused by cytomegalovirus are often encountered. However, doctors are aware of the chronic infection caused by the Epstein-Barr virus (EBV) and its forms. general practice clearly not sufficiently informed.

EBV was first isolated from Burkett's lymphoma cells 35 years ago. It soon became known that the virus can cause acute and acute illness in humans. It has now been established that EBV is associated with a number of oncological, mainly lymphoproliferative and autoimmune diseases (classical, etc.). In addition, EBV can cause chronic manifest and latent forms of the disease, similar to chronic mononucleosis. The Epstein-Barr virus belongs to the family of herpes viruses, a subfamily of gammaherpes viruses and a genus of lymphocryptoviruses, contains two DNA molecules and has the ability, like other viruses of this group, to persist in the human body for life. In some patients, against the background of immune dysfunction and hereditary predisposition to one or another pathology EBV can cause various diseases, which were mentioned above. EBV infects humans by penetrating intact epithelial layers by transcytosis into the underlying lymphoid tissue of the tonsils, in particular B lymphocytes. Penetration of EBV into B lymphocytes occurs through the receptor of these cells CD21, a receptor for the C3d component of complement. Following infection, the number of affected cells increases through virus-dependent cell proliferation. Infected B lymphocytes can remain in the tonsillar crypts for a considerable time, which allows the virus to be released into external environment with saliva.

With infected cells, EBV spreads to other lymphoid tissues and peripheral blood. The maturation of B lymphocytes into plasma cells (which occurs normally when they encounter the corresponding antigen or infection) stimulates the multiplication of the virus, and the subsequent death (apoptosis) of these cells leads to the release of viral particles into the crypts and saliva. In virus-infected cells, two types of reproduction are possible: lytic, that is, leading to death, lysis, of the host cell, and latent, when the number of viral copies is small and the cell is not destroyed. EBV can remain for a long time in B-lymphocytes and epithelial cells of the nasopharyngeal region and salivary glands. In addition, it is capable of infecting other cells: T lymphocytes, NK cells, macrophages, neutrophils, vascular epithelial cells. In the nucleus of the host cell, EBV DNA can form a ring structure - an episome, or be integrated into the genome, causing chromosomal abnormalities.

In acute or active infection, lytic replication of the virus predominates.

Active reproduction of the virus can occur as a result of weakening of immunological control, as well as stimulation of the reproduction of cells infected with the virus under the influence of a number of reasons: acute bacterial or viral infection, vaccination, stress, etc.

According to most researchers, today approximately 80-90% of the population is infected with EBV. Primary infection most often occurs in childhood or young adulthood. The routes of transmission of the virus are different: airborne, household contact, transfusion, sexual, transplacental. After EBV infection, virus replication in the human body and the formation of an immune response can be asymptomatic or manifest as minor signs of acute respiratory viral infection. But if a large amount of infection occurs and/or there is a significant weakening of the immune system during this period, the patient may develop a picture of infectious mononucleosis. There are several possible outcomes of an acute infectious process:

• recovery (virus DNA can only be detected with a special study in single B-lymphocytes or epithelial cells);
• asymptomatic virus carriage or latent infection (the virus is detected in saliva or lymphocytes with a sensitivity of the PCR method of 10 copies in the sample);
• chronic recurrent infection: a) chronic active EBV infection of the type of chronic infectious mononucleosis; b) a generalized form of chronic active EBV infection with damage to the central nervous system, myocardium, kidneys, etc.; c) EBV-associated hemophagocytic syndrome; d) erased or atypical forms of EBV infection: long-term low-grade fever of unknown origin, clinical picture - recurrent bacterial, fungal, often mixed infections of the respiratory and gastrointestinal tract, and other manifestations;
• development of an oncological (lymphoproliferative) process (multiple polyclonal, nasopharyngeal carcinoma, leukoplakia of the tongue and mucous membranes of the oral cavity and intestines, etc.);
• development of autoimmune disease -, etc. (it should be noted that two latest groups diseases can develop over a long period of time after infection);
• According to the results of research in our laboratory (and based on a number of foreign publications), we concluded that EBV may play an important role in the occurrence.

The immediate and long-term prognosis for a patient with acute infection caused by EBV depends on the presence and severity of immune dysfunction, genetic predisposition to certain EBV-associated diseases (see above), as well as from the presence of a number external factors(stress, infections, surgical interventions, adverse environmental influences) that damage the immune system. It was discovered that EBV has a large set of genes that give it the ability to evade the human immune system to a certain extent. In particular, EBV produces proteins that are analogues of a number of human interleukins and their receptors that modify the immune response. During the period of active reproduction, the virus produces IL-10-like protein, which suppresses T-cell immunity, the function of cytotoxic lymphocytes, macrophages, and disrupts all stages of the functioning of natural killer cells (that is, the most important antiviral defense systems). Another viral protein (BI3) can also suppress T-cell immunity and block killer cell activity (via suppression of interleukin-12). Another property of EBV, like other herpes viruses, is high mutability, which allows it to avoid for a certain time the effects of specific immunoglobulins (which were developed for the virus before its mutation) and cells of the host’s immune system. Thus, the reproduction of EBV in the human body can cause the aggravation (emergence) of secondary immunodeficiency.

Clinical forms of chronic infection caused by the Epstein-Barr virus

Chronic active EBV infection (CA EBV) is characterized by a long, relapsing course and the presence of clinical and laboratory signs of viral activity. Patients are concerned about weakness, sweating, often pain in muscles and joints, skin rashes, cough, difficulty nasal breathing, discomfort in the throat, pain, heaviness in the right hypochondrium, previously uncharacteristic headaches for this patient, dizziness, emotional lability, depressive disorders, sleep disturbances, decreased memory, attention, and intelligence. Often observed low-grade fever, enlarged lymph nodes, hepatosplenomegaly of varying severity. Often these symptoms have a wave-like character. Sometimes patients describe their condition as chronic flu.

In a significant proportion of patients with CA VEBI, the addition of other herpetic, bacterial and fungal infections (inflammatory diseases of the upper respiratory tract and gastrointestinal tract) is observed.

CA VEBI is characterized by laboratory (indirect) signs of viral activity, namely relative and absolute lymphomonocytosis, the presence of atypical mononuclear cells, less often monocytosis and lymphopenia, in some cases anemia and thrombocytosis. When studying the immune status of patients with CA VEBI, changes in the content and function of specific cytotoxic lymphocytes, natural killer cells, a violation of the specific humoral response (disimmunoglobulinemia, long-term absence of immunoglobulin G (IgG) production or the so-called lack of seroconversion to the late nuclear antigen of the virus - EBNA are observed, which reflects failure of immunological control of virus replication. In addition, according to our data, more than half of the patients have a reduced ability to stimulate the production of interferon (IFN), increased levels of serum IFN, disimmunoglobulinemia, impaired antibody avidity (their ability to firmly bind to the antigen), decreased content of DR+ lymphocytes, and levels of circulating immune complexes and antibodies to DNA are often increased.

In persons with severe immune deficiency, generalized forms of EBV infection may occur with damage to the central and peripheral nervous systems (development of encephalitis, cerebellar ataxia, polyradiculoneuritis), as well as damage to other internal organs (development of lymphocytic interstitial pneumonitis, severe forms). Generalized forms of EBV infection are often fatal.

EBV-associated hemophagocytic syndrome is characterized by the development of anemia or pancytopenia. Often combined with CA VEBI, infectious mononucleosis and lymphoproliferative diseases. The clinical picture is dominated by intermittent fever, hepatosplenomegaly, lymphadenopathy, pancytopenia or severe anemia, liver dysfunction, and coagulopathy. Hemophagocytic syndrome, which develops against the background of infectious mononucleosis, is characterized by high mortality (up to 35%). The above changes are explained by the hyperproduction of pro-inflammatory cytokines (TNF, IL1 and several others) by T cells infected with the virus. These cytokines activate the phagocyte system (reproduction, differentiation and functional activity) in bone marrow, peripheral blood, liver, spleen, lymph nodes. Activated monocytes and histiocytes begin to engulf blood cells, which leads to their destruction. More subtle mechanisms of these changes are under study.

Erased variants of chronic EBV infection

According to our data, CA VEBI often occurs silently or under the guise of other chronic diseases.

There are two most common forms of latent indolent EBV infection. In the first case, patients are concerned about prolonged low-grade fever of unknown origin, weakness, pain in peripheral lymph nodes, myalgia, arthralgia. The undulation of symptoms is also characteristic. In another category of patients, in addition to the complaints described above, there are markers of secondary immunodeficiency in the form of previously uncharacteristic frequent infections of the respiratory tract, skin, gastrointestinal tract, and genitals, which do not completely go away with therapy or quickly recur. Most often in the anamnesis of these patients there are long-term stressful situations, excessive mental and physical overload, less often - a passion for fasting, fashionable diets, etc. Often the above-described condition developed after previous sore throat, acute respiratory infections, influenza-like illness. This variant of infection is also characterized by the persistence and duration of symptoms - from six months to 10 years or more. Repeated examinations reveal EBV in saliva and/or peripheral blood lymphocytes. As a rule, repeated in-depth examinations carried out in most of these patients do not reveal other causes of prolonged low-grade fever and the development of secondary immunodeficiency.

The fact that in the case of sustained suppression of viral replication, long-term remission can be achieved in most patients is also very important for diagnosing CA VEBI. Diagnosis of CA VEBI is difficult due to the lack of specific clinical markers of the disease. A certain “contribution” to underdiagnosis is also made by the lack of awareness of practitioners about this pathology. However, given the progressive nature of CA VEBI, as well as the seriousness of the prognosis (risk of developing lymphoproliferative and autoimmune diseases, high mortality with the development of hemophagocytic syndrome), if CA VEBI is suspected, it is necessary to conduct an appropriate examination. The most characteristic clinical symptom complex in CA VEBI is prolonged low-grade fever, weakness and decreased performance, sore throat, lymphadenopathy, hepatosplenomegaly, liver dysfunction, mental disorders. An important symptom is the lack of full clinical effect from conventional therapy for asthenic syndrome, restorative therapy, as well as from the prescription of antibacterial drugs.

When carrying out differential diagnosis of CA VEBI, the following diseases should first be excluded:

• other intracellular, including viral infections: HIV, viral hepatitis, cytomegalovirus infection, toxoplasmosis, etc.;
• rheumatic diseases, including those associated with EBV infection;
• oncological diseases.

Laboratory tests in the diagnosis of EBV infection

• Clinical blood test: slight leukocytosis, lymphomonocytosis with atypical mononuclear cells, in some cases hemolytic anemia due to hemophagocytic syndrome or autoimmune anemia, possibly thrombocytopenia or thrombocytosis may be observed.
• Biochemical blood test: increased levels of transaminases, LDH and other enzymes, acute phase proteins, such as CRP, fibrinogen, etc. are detected.

As mentioned above, all of the listed changes are not strictly specific to EBV infection (they can also be found in other viral infections).

• Immunological examination: it is advisable to evaluate the main indicators of antiviral protection: the state of the interferon system, the level of immunoglobulins of the main classes, the content of cytotoxic lymphocytes (CD8+), T-helper cells (CD4+).

According to our data, two types of changes occur in the immune status during EBV infection: increased activity of individual parts of the immune system and/or imbalance and insufficiency of others. Signs of tension of antiviral immunity can be increased levels of IFN in the blood serum, IgA, IgM, IgE, CIC, often the appearance of antibodies to DNA, an increase in the content of natural killer cells (CD16+), T-helper cells (CD4+) and/or cytotoxic lymphocytes (CD8+) . The phagocyte system can be activated.

In turn, immune dysfunction/insufficiency in this infection is manifested by a decrease in the ability to stimulate the production of IFN alpha and/or gamma, disimmunoglobulinemia (decreased IgG content, less often IgA, increased Ig M content), decreased antibody avidity (their ability to firmly bind to the antigen) , a decrease in the content of DR+ lymphocytes, CD25+ lymphocytes, that is, activated T cells, a decrease in the number and functional activity of natural killer cells (CD16+), T helper cells (CD4+), cytotoxic T lymphocytes (CD8+), a decrease in the functional activity of phagocytes and/or change (perversion) of their reaction to stimuli, including immunocorrectors.

• Serological studies: an increase in antibody titers (AT) to antigens (AG) of the virus is a criterion for the presence of an infectious process at the present time or evidence of contact with an infection in the past. During acute EBV infection, depending on the stage of the disease, different classes of antibodies to virus antigens are detected in the blood, and “early” antibodies change to “late” ones.

Specific IgM antibodies appear in the acute phase of the disease or during an exacerbation and usually disappear after four to six weeks. IgG-Abs to EA (early) also appear in the acute phase, are markers of active viral replication and, upon recovery, decrease over three to six months. IgG antibodies to VCA (early) are detected in the acute period with a maximum in the second to fourth week, then their number decreases, and the threshold level remains for a long time. IgG antibodies to EBNA are detected two to four months after the acute phase, and their production continues throughout life.

According to our data, with CA EBNA, “early” IgG-ABs are detected in the blood of more than half of patients, while specific IgM-ABs are detected much less frequently, while the content of late IgG-ABs to EBNA fluctuates depending on the stage of exacerbation and state of immunity.

It should be noted that conducting a serological study over time helps in assessing the state of the humoral response and the effectiveness of antiviral and immunocorrective therapy.

• DNA diagnostics CA WEBI. Using the polymerase chain reaction (PCR) method, EBV DNA is determined in various biological materials: saliva, blood serum, leukocytes and peripheral blood lymphocytes. If necessary, research is carried out in biopsy samples of the liver, lymph nodes, intestinal mucosa, etc. The PCR diagnostic method, characterized by high sensitivity, has found application in many areas, for example in forensics: in particular, in cases where it is necessary to identify minimal trace amounts of DNA .

The use of this method in clinical practice to detect a particular intracellular agent is often difficult due to its too high sensitivity, since it is not possible to distinguish a healthy carrier (minimal amount of infection) from manifestations of an infectious process with active reproduction of the virus. Therefore, for clinical studies, a PCR technique with a given, lower sensitivity is used. As our studies have shown, the use of a method with a sensitivity of 10 copies per sample (1000 GE/ml in 1 ml of sample) makes it possible to identify healthy EBV carriers, while reducing the sensitivity of the method to 100 copies (10,000 GE/ml in 1 ml of sample) gives the ability to diagnose individuals with clinical and immunological signs of CA VEBI.

We observed patients with clinical and laboratory data (including the results of serological tests) characteristic of a viral infection, in whom, during the initial examination, the analysis for EBV DNA in saliva and blood cells was negative. It is important to note that in these cases it is impossible to exclude the replication of the virus in the gastrointestinal tract, bone marrow, skin, lymph nodes, etc. Only a repeated examination over time can confirm or exclude the presence or absence of CA VEBI.

Thus, to make a diagnosis of CA VEBI, in addition to a general clinical examination, it is necessary to study the immune status (antiviral immunity), DNA, diagnose the infection in various materials over time, serological studies(ELISA).

Treatment of chronic Epstein-Barr virus infection

Currently, there are no generally accepted treatment regimens for CA VEBI. However, modern ideas about the effect of EBV on the human body and data on the existing risk of developing serious, often fatal diseases show the need for therapy and clinical observation in patients suffering from CA VEBI.

Literature data and the experience of our work allow us to give pathogenetically substantiated recommendations for the treatment of CA VEBI. In the complex treatment of this disease, the following drugs are used:

• , in some cases in combination with IFN inducers - (creation of an antiviral state of uninfected cells, suppression of virus reproduction, stimulation of natural killer cells, phagocytes);
• abnormal nucleotides (suppress the reproduction of the virus in the cell);
• immunoglobulins for intravenous administration (blockade of “free” viruses found in the intercellular fluid, lymph and blood);
• analogues of thymic hormones (promote the functioning of the T-link, in addition, stimulates phagocytosis);
• glucocorticoids and cytostatics (reduce viral replication, inflammatory response and organ damage).

Other groups of drugs, as a rule, play a supporting role.

Before starting treatment, it is advisable to examine the patient’s family members for the release of viruses (in saliva) and the possibility of re-infection of the patient; if necessary, suppression of viral replication is also carried out in family members.

• The volume of therapy for patients with chronic active EBV infection (CA EBV) may vary, depending on the duration of the disease, the severity of the condition and immune disorders. Treatment begins with the administration of antioxidants and detoxification. In moderate and severe cases, it is advisable to carry out the initial stages of therapy in a hospital setting.

The drug of choice is interferon-alpha, which is prescribed as monotherapy in moderate cases. The domestic recombinant drug Reaferon has proven itself well (in terms of biological activity and tolerability), and its cost is significantly lower than that of foreign analogues. The doses of IFN-alpha used vary depending on weight, age, and drug tolerance. The minimum dose is 2 million units per day (1 million units twice a day intramuscularly), daily for the first week, then three times a week for three to six months. Optimal doses are 4-6 million units (2-3 million units twice a day).

IFN-alpha, as a pro-inflammatory cytokine, can cause flu-like symptoms (fever, headaches, dizziness, myalgia, arthralgia, vegetative disorders - changes in blood pressure, heart rate, less often, dyspeptic symptoms).

The severity of these symptoms depends on the dose and individual tolerance of the drug. These are transient symptoms (disappear 2-5 days after the start of treatment), and some of them are controlled by the prescription of non-steroidal anti-inflammatory drugs. When treated with IFN-alpha drugs, reversible thrombocytopenia, neutropenia, skin reactions (itching, rashes of various types), and rarely, alopecia may occur. Long-term use of IFN-alpha in large doses ah can lead to immune dysfunction, clinically manifested by furunculosis and other pustular and viral skin lesions.

In moderate and severe cases, as well as when IFN-alpha drugs are ineffective, it is necessary to add abnormal nucleotides to treatment - valacyclovir (Valtrex), ganciclovir (Cymevene) or famciclovir (Famvir).

The course of treatment with abnormal nucleotides should be at least 14 days, the first seven days preferably intravenous administration of the drug.

In cases of severe CAEBI, complex therapy also includes immunoglobulin preparations for intravenous administration in a dose of 10-15 g. If necessary (based on the results of an immunological examination), immunocorrectors with T-activating ability or replacement thymic hormones (thymogen, immunofan, tactivin, etc.) for one to two months with gradual withdrawal or switching to maintenance doses (twice a week).

Treatment of EBV infection must be carried out under the supervision of a clinical blood test (once every 7-14 days), a biochemical analysis (once a month, more often if necessary), and an immunological study - after one to two months.

• Treatment of patients with generalized EBV infection is carried out in a hospital, together with a neurologist.

Antiviral therapy with IFN-alpha drugs and abnormal nucleotides primarily includes systemic corticosteroids in doses: parenteral (in terms of prednisolone) 120-180 mg per day, or 1.5-3 mg/kg, it is possible to use pulse therapy with metipred 500 mg IV drip, or orally 60-100 mg per day. Plasma and/or immunoglobulin preparations for intravenous administration are administered intravenously. In case of severe intoxication, the introduction of detoxifying solutions, plasmapheresis, hemosorption, and the administration of antioxidants are indicated. In severe cases, cytostatics are used: etoposide, cyclosporine (Sandimmune or Consupren).

• Treatment of patients with EBV infection complicated by HFS must be carried out in a hospital. If the leading clinical picture and life prognosis is HPS, therapy begins with the prescription of large doses of corticosteroids (blockade of the production of proinflammatory cytokines and phagocytic activity), in the most severe cases with cytostatics (etoposide, cyclosporine) against the background of the use of abnormal nucleotides.
• Treatment of patients with latent erased EBV infection can be carried out on an outpatient basis; therapy includes the administration of interferon-alpha (possibly alternating with IFN inducer drugs). If the effectiveness is insufficient, abnormal nucleotides and immunoglobulin preparations for intravenous administration are used; Based on the results of an immunological examination, immunocorrectors (T-activators) are prescribed. In cases of so-called “carriage”, or “asymptomatic latent infection” with the presence of a specific immune response to the multiplication of the virus, observation and laboratory control are carried out ( clinical analysis blood, biochemistry, PCR diagnostics, immunological examination) after three to four months.

Treatment is prescribed when clinical symptoms of EBV infection appear or when signs of VID develop.

Carrying out complex therapy including the above drugs makes it possible to achieve remission of the disease in some patients with a generalized form of the disease and hemophagocytic syndrome. In patients with moderate manifestations of CA VEBI and in cases of an erased course of the disease, the effectiveness of therapy is higher (70-80%), in addition to the clinical effect, it is often possible to suppress viral replication.

After suppressing viral replication and obtaining a clinical effect, it is important to prolong remission. Sanatorium-resort treatment is indicated.

Patients should be informed about the importance of maintaining a work-rest schedule, good nutrition, and limiting/cessation of alcohol intake; in the presence of stressful situations, the help of a psychotherapist is necessary. In addition, if necessary, maintenance immunocorrective therapy is carried out.

Thus, the treatment of patients with chronic Epstein-Barr virus infection is complex, carried out under laboratory control and includes the use of interferon-alpha drugs, abnormal nucleotides, immunocorrectors, immunotropic replacement drugs, glucocorticoid hormones, and symptomatic agents.

Literature

1. Gurtsevich V. E., Afanasyeva T. A. Genes of latent Epstein-Barr infection (EBV) and their role in the occurrence of neoplasia // Russian Journal<ВИЧ/СПИД и родственные проблемы>. 1998; T. 2, No. 1: 68-75.
2. Didkovsky N. A., Malashenkova I. K., Tazulakhova E. B. Interferon inducers are a new promising class of immunomodulators // Allergology. 1998. No. 4. P. 26-32.
3. Egorova O. N., Balabanova R. M., Chuvirov G. N. The significance of antibodies to herpetic viruses determined in patients with rheumatic diseases// Therapeutic archive. 1998. No. 70(5). pp. 41-45.
4. Malashenkova I.K., Didkovsky N.A., Govorun V.M., Ilyina E.N., Tazulakhova E.B., Belikova M.M., Shchepetkova I.N. On the role of the Epstein-Barr virus in development of chronic fatigue syndrome and immune dysfunction.
5. Christian Brander and Bruce D Walker Modulation of host immune responses by clinically relevant human DNA and RNA viruses // Current Opinion in Microbiology 2000, 3: 379-386.
6. Cruchley A. T., Williams D. M., Niedobitek G. Epstein-Barr virus: biology and disease // Oral Dis 1997 May; 3 Suppl 1: S153-S156.
7. Glenda C. Faulkner, Andrew S. Krajewski and Dorothy H. CrawfordA The ins and outs of EBV infection // Trends in Microbiology. 2000, 8: 185-189.
8. Jeffrey I. Cohen The biology of Epstein-Barr virus: lessons learned from the virus and the host // Current Opinion in Immunology. 1999. 11: 365-370.
9. Kragsbjerg P. Chronic active mononucleosis // Scand. J. Infect. Dis. 1997. 29(5): 517-518.
10. Kuwahara S., Kawada M., Uga S., Mori K. A case of cerebellar meningo-encephalitis caused by Epstein-Barr virus (EBV): usefulness of Gd-enhanced MRI for detection of the lesions // No To Shinkei. 2000. Jan. 52(1): 37-42.
11. Lekstron-Himes J. A., Dale J. K., Kingma D. W. Periodic illness associated with Epstein-Barr virus infection // Clin. Infect. Dis. Jan. 22(1): 22-27.
12. Okano M. Epstein-Barr virus infection and its role in the expanding spectrum of human diseases // Acta Paediatr. 1998. Jan; 87(1): 11-18.
13. Okuda T., Yumoto Y. Reactive hemophagocytic syndrome responded to combination chemotherapy with steroid pulse therapy // Rinsho Ketsueki. 1997. Aug; 38(8): 657-62.
14. Sakai Y., Ohga S., Tonegawa Y. Interferon-alpha therapy for chronic active Epstein-Barr virus infection // Leuk. Res. 1997 Oct; 21(10): 941-50.
15. Yamashita S., Murakami C., Izumi Y. Severe chronic active Epstein-Barr virus infection accompanied by virus-associated hemophagocytic syndrome, cerebellar ataxia and encephalitis // Psychiatry Clin. Neurosci. 1998. Aug; 52(4): 449-52.

I. K. Malashenkova, Candidate of Medical Sciences

N. A. Didkovsky,Doctor of Medical Sciences, Professor

J. S. Sarsania, Candidate of Medical Sciences

M. A. Zharova, E. N. Litvinenko, I. N. Shchepetkova, L. I. Chistova, O. V. Pichuzhkina

Research Institute of Physico-Chemical Medicine of the Ministry of Health of the Russian Federation

T. S. Guseva, O. V. Parshina

State Research Institute of Epidemiology and Microbiology named after. N. F. Gamaleyi RAMS, Moscow

Clinical illustration of a case of chronic active EBV infection with hemophagocytic syndrome

Patient I.L., 33 years old, applied to the laboratory of clinical immunology of the Research Institute of Physics and Chemistry on March 20, 1997 with complaints of prolonged low-grade fever, severe weakness, sweating, sore throat, dry cough, headaches, shortness of breath when moving, rapid heartbeat, sleep disturbances, emotional lability (increased irritability, touchiness, tearfulness), forgetfulness.

From the anamnesis: in the fall of 1996, after a severe sore throat (accompanied by severe fever, intoxication, lymphadenopathy), the above complaints arose, an increase in ESR, changes in the leukocyte formula (monocytosis, leukocytosis) persisted for a long time, and anemia was detected. Outpatient treatment (antibiotic therapy, sulfonamides, iron supplements, etc.) turned out to be ineffective. The condition progressively worsened.

On admission: body temperature - 37.8°C, skin high humidity, pronounced pallor of the skin and mucous membranes. Lymph nodes (submandibular, cervical, axillary) are enlarged to 1-2 cm, have a dense elastic consistency, are painful, and are not fused with the surrounding tissues. The pharynx is hyperemic, swollen, signs of pharyngitis, tonsils are enlarged, loose, moderately hyperemic, the tongue is covered with a white-gray coating, hyperemic. In the lungs there is a harsh tinge of breathing, scattered dry wheezing on inspiration. The borders of the heart: the left is enlarged by 0.5 cm to the left of the midclavicular line, heart sounds are preserved, short systolic murmur above the apex, irregular rhythm, extrasystole (5-7 per minute), heart rate - 112 per minute, blood pressure - 115/70 mmHg Art. The abdomen is swollen, moderately painful on palpation in the right hypochondrium and along the colon. According to ultrasound of the abdominal organs, there is a slight increase in the size of the liver and, to a slightly greater extent, the spleen.

From laboratory tests, noteworthy was normochromic anemia with a decrease in Hb to 80 g/l with anisocytosis, poikilocytosis, polychromatophilia of erythrocytes; reticulocytosis, normal serum iron content (18.6 µm/l), negative reaction Coombs. In addition, leukocytosis, thrombocytosis and monocytosis with a large number of atypical mononuclear cells, and accelerated ESR were observed. Biochemical blood tests showed a moderate increase in transaminases and CPK. ECG: sinus rhythm, irregular, atrial and ventricular extrasystole, heart rate up to 120 per minute. The electrical axis of the heart is deviated to the left. Violation of intraventricular conduction. Reduced voltage in standard leads, diffuse changes in the myocardium, in chest leads changes characteristic of myocardial hypoxia were observed. The immune status was also significantly impaired - the content of immunoglobulin M (IgM) was increased and immunoglobulins A and G (IgA and IgG) were reduced, there was a predominance of the production of low-avidity, that is, functionally inferior antibodies, dysfunction of the T-link of immunity, increased levels of serum IFN, decreased ability to IFN production in response to many stimuli.

The titers of IgG antibodies to early and late viral antigens (VCA, EA EBV) were increased in the blood. During a virological study (over time) using the polymerase chain reaction (PCR) method, EBV DNA was detected in peripheral blood leukocytes.

During this and subsequent hospitalizations, an in-depth rheumatological examination and oncological search were carried out; other somatic and infectious diseases were also excluded.

The patient was given the following diagnoses: chronic active EBV infection, moderate hepatosplenomegaly, focal myocarditis, somatogenically caused persistent; virus-associated hemophagocytic syndrome. Immunodeficiency state; chronic pharyngitis, bronchitis of mixed viral and bacterial etiology; , enteritis, dysbiosis of intestinal flora.

Despite the conversation, the patient categorically refused the administration of glucocorticoids and interferon-alpha drugs. Treatment was carried out, including antiviral therapy (Virolex intravenously for a week, with a transition to Zovirax 800 mg 5 times a day per os), immunocorrective therapy (Thymogen according to the regimen, Cycloferon 500 mg according to the regimen, Immunofan according to the regimen), replacement therapy (Octagam 2.5 g twice intravenously), detoxification measures (hemodez infusions, enterosorption), antioxidant therapy (tocoferrol, ascorbic acid), metabolic drugs were used (Essentiale, Riboxin), vitamin therapy (multivitamins with microelements) was prescribed.

After treatment, the patient’s temperature returned to normal, weakness and sweating decreased, and some indicators of immune status improved. However, it was not possible to completely suppress virus replication (EBV continued to be detected in leukocytes). Clinical remission did not last long - after a month and a half, a re-exacerbation occurred. During the study, in addition to signs of activation of a viral infection, anemia, and accelerated ESR, high titers of antibodies to salmonella were detected. Outpatient treatment of the main and concomitant diseases was carried out. A severe exacerbation began in January 1998 after acute bronchitis and pharyngitis. According to laboratory studies, during this period there was a worsening of anemia (up to 76 g/l) and an increase in the number of atypical mononuclear cells in the blood. An increase in hepatosplenomegaly was noted; Chlamidia Trachomatis, Staphylococcus aureus, streptococcus, in the urine - Ureaplasma Urealiticum, a significant increase in antibody titers to EBV, CMV, herpes simplex virus type 1 (HSV 1) was detected in the blood. Thus, the patient’s number of concomitant infections increased, which also indicated an increase in immune deficiency. Therapy was carried out with interferon inducers, replacement therapy with T-activators, antioxidants, metabolites, and long-term detoxification. A noticeable clinical and laboratory effect was achieved by June 1998, the patient was recommended to continue metabolic, antioxidant, and immunoreplacement therapy (thymogen, etc.). When re-examined in the fall of 1998, EBV was not detected in saliva and lymphocytes, although moderate anemia and immune dysfunction persisted.

Thus, in patient I., 33 years old, acute EBV infection took a chronic course and was complicated by the development of hemophagocytic syndrome. Despite the fact that it was possible to achieve clinical remission, the patient needs dynamic monitoring in order to both control EBV replication and timely diagnosis of lymphoproliferative processes (given the high risk of their development).

Note!

• EBV was first isolated from Burkett's lymphoma cells 35 years ago.
• Epstein-Barr virus belongs to the herpes virus family.
• Today, approximately 80-90% of the population is infected with EBV.
• Reproduction of EBV in the human body can cause aggravation (occurrence) of secondary immunodeficiency.

Most researchers of the Epstein Barr virus (EBV) classify it as a member of the herpesvirus type 4 family. This type of herpesvirus is considered the most common in the world, since 99% of the adult population and approximately 60% of children over 1 year of age are its carriers. It is worth immediately noting that carriers of the Epstein Barr virus, as a rule, do not suffer from diseases that can be caused by this virus if their immune system functions normally. However, in some cases, the Ebstein-Barr virus can lead to the development of acute damage to various organs and systems of the body.

This virus was discovered back in 1960, but the pathogenicity of the virus and other characteristics have been studied relatively recently. This type of herpes virus has a rather complex structure and is spherical in shape. It was recently found that most children under 16 years of age experience mild forms of illness caused by EBV. As a rule, these diseases occur in mild form colds or intestinal disorders that are not life-threatening. After experiencing the acute phase of the disease, the body acquires stable immunity to the virus. However, in some cases, serious damage to internal organs may occur, so at the first manifestations of the disease, you should urgently seek medical help to conduct a blood test for the presence of the virus.

Currently, the reasons for the defeat of such a significant number of people by this virus are unknown, but researchers of the virus point to the unique structure of this microorganism, which includes more than 85 protein proteins that contain the DNA of the virus. The high pathogenicity of the virus and its ability to quickly penetrate host cells and begin to multiply are explained by the fact that the virus for a long time can be without a host and transmitted not only by contact, but also by airborne droplets.

Many researchers of the Epstein Barr virus agree that this virus is dangerous not in its ability to cause diseases characterized by an acute course, but in the fact that, under certain conditions, the pathogenic DNA of the EBV virus can lead to the development malignant tumors. There are a number of diseases that develop, as a rule, against the background of organ damage by the Ebstein-Barr virus:

• Infectious mononucleosis;
• chronic fatigue syndrome;
• lymphogranulomatosis;
• general immunological deficiency;
• herpes;
• systemic hepatitis;
• malignant neoplasms in the nasopharynx;
• malignant tumors in the intestines and stomach;
• damage to the spinal cord or brain;
• malignant tumors of the salivary glands;
• lymphoma;
• leukoplakia of the oral cavity.

Among other things, the presence of EBV can provoke the development of bacterial and fungal diseases. The course of diseases caused by the EBV virus can be complicated by paratonsillitis, otitis media, splenic rupture, renal failure, pancreatitis, respiratory failure, myocarditis. Currently, there is no clear classification of the manifestations of the course of diseases caused by this herpes virus, so doctors use a vague classification, which involves the designation of general characteristic features development and course of existing pathology. As a rule, the following parameters are determined: time of infection, form of the disease, severity of the disease, activity phase, presence of complications, etc.

What symptoms can Epstein Barr virus cause?

The symptoms observed with EBV are extremely diverse and largely depend on which organs and systems of the body were affected. All EBV symptoms formally can be divided into general and specific. Common symptoms of damage to the body by the Epstein-Barr virus include:

• chills;
• increased body temperature;
• weakness;
• body aches;
• swollen lymph nodes;
• rash on the skin;
• signs of inflammation in the throat;
• redness of the throat;
• a sore throat.

Usually, general symptoms are observed only in case of an acute reaction of the body to primary infection. If the disease occurs against a background of reduced immunity, as damage to individual organs and systems develops, symptoms of an inflammatory process may appear in the kidneys, liver, heart and other organs. When the virus affects the nervous system, severe pain, impaired motor ability of individual muscles, contractures, paresis and many other manifestations cannot be ruled out.

The incubation period of the Epstein-Barr virus lasts about 4-5 weeks, therefore, if a group of children has been diagnosed with mononucleosis, most likely, other children who maintain contact with the sick child will also become ill.

After the incubation period, patients immediately experience an increase in body temperature and general symptoms.

It is very important at this time to visit a doctor and get qualified advice regarding treatment and do a blood test, since with improper therapy not only serious complications can develop, but also chronic form diseases.

Diagnosis and treatment of diseases caused by the Epstein Barr virus

In most cases, patients consult a doctor already having a number of characteristic symptoms. This allows you to determine the presence of a viral infection. Diagnosis of the Epstein Barr virus in the body involves a number of studies. First of all, a blood test is done to detect the titer of IgM antibodies. A blood test with an elevated titer of 1:40 is a diagnostic criterion for EBV damage to the body. A similar titer is characteristic of mononucleosis.

Once the basic blood test is done, polymerase chain reaction and enzyme immunoassay may also be performed. After a complete diagnosis of the patient’s condition has been made, a course of treatment can be prescribed. Despite the fact that the human liver produces a special immunoglobulin against the virus, in the presence of an acute phase of the course it is necessary to take medications aimed at treating the symptoms. Pregnancy and the course of the disease with severe complications are the reason for inpatient treatment. It is worth immediately noting that pregnancy can be saved if future mom got sick with mononucleosis. However, the risk of infection of the fetus and transmission of the virus to the child increases, so in this case it is very important to undergo the correct course of treatment so that the pregnancy continues without complications. In cases where the course of the disease is not complicated, patients are treated on an outpatient basis.

The basis of treatment is various kinds of antiviral and immunomodulating drugs that can quickly eliminate foci of viral infection. Important role Medicines aimed at eliminating symptoms play a role in alleviating the patient’s condition, that is, antipyretics, painkillers, antiallergic drugs, gargles, vitamin complexes. As additional treatments, decoctions of chamomile, coltsfoot, mint, oak root, ginseng, calendula, etc. can be used.

During the active phase of the disease, patients are prescribed bed rest and complete rest. The duration of treatment ranges from 2 weeks to several months.